Perforin-dependent cytotoxic activity and lymphokine secretion by CD4+ T cells are regulated by CD8+ T cells
ABSTRACT Factors influencing the development of CD4+ T cell subpopulations with differing lymphokine profiles are well established. However, CD4+ cells can show both perforin- and Fas ligand-dependent cytotoxicity, and little is known about conditions favoring the development of these effector activities. We now report that CD8+ cells regulate the development of perforin-dependent cytotoxicity in CD4+ cells. CD4+ cells activated in either the presence or absence of CD8+ cells developed Fas ligand-dependent cytotoxic activity. However, CD4+ cells developed perforin-dependent cytotoxicity only in the absence of activated CD8+ cells. CD8+ cells also inhibited the development of IL-4-secreting CD4+ cells; however, there was no correlation between the expression of perforin-dependent cytotoxic activity and the ability to secrete IL-4, and perforin-dependent cytotoxic CD4+ cells represented only 10% of isolated clones. This suggests that the two characteristics are expressed in different CD4+ subsets and might be regulated by distinct effects of the CD8+ cells. In keeping with this, regulation of the lymphokine profile of CD4+ cells by CD8+ cells was consistent with mediation by IFN-gamma, but only when delivered at high concentrations requiring close proximity of the cells. In contrast, regulation of perforin-dependent cytotoxic activity of CD4+ cells by CD8+ cells seemed inconsistent with an IFN-gamma-dependent mechanism, suggesting either direct cell contact or close proximity to allow delivery of an unidentified soluble factor. The characteristics of perforin-dependent CD4+ CTL and their regulation by activated CD8+ cells suggest that they represent a previously unrecognized subpopulation that plays a defensive role when a CD8+ cell response is absent.
- SourceAvailable from: Susan L Swain
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- "One of the challenges of identifying ThCTL in situ is that they are overshadowed and seemingly inhibited by the presence of CD8 CTL which outnumber them  . Thus it is not surprising that ThCTL have also been identified in virally infected mice deficient in, or depleted of, CD8 T cells. "
ABSTRACT: CD4 T cells that acquire cytotoxic phenotype and function have been repeatedly identified in humans, mice, and other species in response to many diverse pathogens. Since CD4 cytotoxic T cells are able to recognize antigenic determinants unique from those recognized by the parallel CD8 cytotoxic T cells, they can potentially contribute additional immune surveillance and direct effector function by lysing infected or malignant cells. Here, we briefly review much of what is known about the generation of cytotoxic CD4 T cells and describe our current understanding of their role in antiviral immunity. Furthering our understanding of the many roles of CD4 T cells during an anti-viral response is important for developing effective vaccine strategies that promote long-lasting protective immunity.BioMed Research International 11/2011; 2011:954602. DOI:10.1155/2011/954602 · 2.71 Impact Factor
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- "13-7, 13-9 and 13-10, with permission from Elsevier.) response . B-cell production of virus-specific antibodies  and CTL-mediated cytolytic activity  are stimulated in T helper type 1 responses. "
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ABSTRACT: Corneal allografts are the oldest, most common, and most successful transplants performed on humans and animals. The cornea is endowed with a constellation of unique factors that contribute to its immune privilege and the low incidence of immune rejection. In spite of this immune privilege, 10 percent of first-time corneal grafts will undergo immune rejection. Several novel therapeutic strategies hold promise for modulating the alloimmune response by either promoting antigen-specific tolerance or redirecting the host's response from a Th1 pathway toward a Th2 pathway.International Reviews Of Immunology 08/2009; 21(2-3):173-96. DOI:10.1080/08830180212064 · 5.28 Impact Factor